An Interaction between RRP6 and SU(VAR)3-9 Targets RRP6 to Heterochromatin and Contributes to Heterochromatin Maintenance in

English version České info

Cells regulate the packaging of DNA in the chromatin, and an important process in the development of any eukaryote is the definition of chromatin states. Heterochromatin is a condensed form of chromatin that is usually silent. Short non-coding RNAs participate in the silencing of transposons in animal germ cells and in the establishment of heterochromatin states during early development. These non-coding RNAs guide histone methyltransferases to the histones in the chromatin, which in turn creates binding sites for other factors that keep the heterochromatin condensed. The non-coding RNAs that participate in the establishment of heterochromatic domains are active in germ cells and gonads, and other mechanisms must exist in animal somatic tissues to maintain the established patterns of heterochromatin throughout development. Here, we identify RRP6 as a protein that is necessary for maintaining the condensed state of heterochromatin in a subset of heterochromatic loci in the somatic fruitfly genome. RRP6 is a ribonuclease that plays many roles in RNA processing and in quality control of gene expression. We show that RRP6 is tethered to heterochromatin through an interaction with a histone methyltransferase, and that in the heterochromatin RRP6 acts on transcripts derived from repetitive sequences that need to be degraded to maintain the packaging of the heterochromatin. The importance of ribonucleases for the structure of the heterochromatin had been shown in yeast cells. Our findings show that RNA degradation participates in chromatin silencing also in animal cells.

Vyšlo v časopise: An Interaction between RRP6 and SU(VAR)3-9 Targets RRP6 to Heterochromatin and Contributes to Heterochromatin Maintenance in. PLoS Genet 11(9): e32767. doi:10.1371/journal.pgen.1005523
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005523

Souhrn

Zdroje

1. Hoskins R.A., Carlson J.W., Kennedy C., Acevedo D., Evans-Holm M., et al. (2007). Sequence finishing and mapping of Drosophila melanogaster heterochromatin. Science 316, 1625–1628. 17569867

2. Lucchesi J.C. (2011). Drosophila Epigenetics. In: Handbook of Epigenetics: The New Molecular and Medical Genetics. Elsevier Inc, 203–232.

3. Elgin S.C., and Reuter G. (2013). Position-effect variegation, heterochromatin formation, and gene silencing in Drosophila. Cold Spring Harb Perspect Biol 5, a017780. doi: 10.1101/cshperspect.a017780 23906716

4. Grewal S.I., and Elgin S.C. (2007). Transcription and RNA interference in the formation of heterochromatin. Nature 447, 399–406. 17522672

5. Lachner M., O'Carroll D., Rea S., Mechtler K., and Jenuwein T. (2001). Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410, 116–120. 11242053

6. Piacentini L., Fanti L., Negri R., Del Vescovo V., Fatica A., et al. (2009). Heterochromatin protein 1 (HP1a) positively regulates euchromatic gene expression through RNA transcript association and interaction with hnRNPs in Drosophila. PLoS genetics 5, e1000670. doi: 10.1371/journal.pgen.1000670 19798443

7. Keller C., Adaixo R., Stunnenberg R., Woolcock K.J., Hiller S., et al. (2012). HP1(Swi6) mediates the recognition and destruction of heterochromatic RNA transcripts. Molecular cell 47, 215–227. doi: 10.1016/j.molcel.2012.05.009 22683269

8. Castel S.E., and Martienssen R.A. (2013). RNA interference in the nucleus: roles for small RNAs in transcription, epigenetics and beyond. Nat Rev Genet 14, 100–112. doi: 10.1038/nrg3355 23329111

9. Bühler M., Verdel A., and Moazed D. (2006). Tethering RITS to a nascent transcript initiates RNAi -⁠ and heterochromatin-dependent gene silencing. Cell 125, 873–886. 16751098

10. Zhang H., and Zhu J.K. (2011). RNA-directed DNA methylation. Curr Opin Plant Biol 14, 142–147. doi: 10.1016/j.pbi.2011.02.003 21420348

11. Lin H., and Yin H. (2008). A novel epigenetic mechanism in Drosophila somatic cells mediated by Piwi and piRNAs. Cold Spring Harb Symp Quant Biol 73, 273–281. doi: 10.1101/sqb.2008.73.056 19270080

12. Huang X.A., Yin H., Sweeney S., Raha D., Snyder M., et al. (2013). A major epigenetic programming mechanism guided by piRNAs. Dev Cell 24, 502–516. doi: 10.1016/j.devcel.2013.01.023 23434410

13. Le Thomas A., Rogers A.K., Webster A., Marinov G.K., Liao S.E., et al. (2013). Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state. Genes Dev. 27, 390–399. doi: 10.1101/gad.209841.112 23392610

14. Rozhkov N.V., Hammell M., and Hannon G.J. (2013). Multiple roles for Piwi in silencing Drosophila transposons. Genes Dev. 27, 400–412. doi: 10.1101/gad.209767.112 23392609

15. Sentmanat M.F., and Elgin S.C. (2012). Ectopic assembly of heterochromatin in Drosophila melanogaster triggered by transposable elements. Proceedings of the National Academy of Sciences of the United States of America 109, 14104–14109. doi: 10.1073/pnas.1207036109 22891327

16. Gu T., and Elgin S.C. (2013). Maternal depletion of Piwi, a component of the RNAi system, impacts heterochromatin formation in Drosophila. PLoS genetics 9, e1003780. doi: 10.1371/journal.pgen.1003780 24068954

17. Houseley J., LaCava J., and Tollervey D. (2006). RNA-quality control by the exosome. Nat Rev Mol Cell Biol 7, 529–539. 16829983

18. Lykke-Andersen S., Tomecki R., Jensen T.H., and Dziembowski A. (2011). The eukaryotic RNA exosome: same scaffold but variable catalytic subunits. RNA Biol 8, 61–66. 21289487

19. Chlebowski A., Lubas M., Jensen T.H., and Dziembowski A. (2013). RNA decay machines: the exosome. Biochimica et biophysica acta 1829, 552–560. doi: 10.1016/j.bbagrm.2013.01.006 23352926

20. Andrulis E.D., Werner J., Nazarian A., Erdjument-Bromage H., Tempst P., et al. (2002). The RNA processing exosome is linked to elongating RNA polymerase II in Drosophila. Nature 420, 837–841. 12490954

21. Schmid M., and Jensen T.H. (2008). The exosome: a multipurpose RNA-decay machine. Trends in biochemical sciences 33, 501–510. doi: 10.1016/j.tibs.2008.07.003 18786828

22. Eberle A. B. and Visa N. (2014). Quality control of mRNP biogenesis: networking at the transcription site. Semin Cell Dev Biol 32 : 37–46. doi: 10.1016/j.semcdb.2014.03.033 24713468

23. Wyers F., Rougemaille M., Badis G., Rousselle J.C., Dufour M.E., et al. (2005). Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell 121, 725–737. 15935759

24. Chekanova J.A., Gregory B.D., Reverdatto S.V., Chen H., Kumar R., et al. (2007). Genome-wide high-resolution mapping of exosome substrates reveals hidden features in the Arabidopsis transcriptome. Cell 131, 1340–1353. 18160042

25. Preker P., Nielsen J., Kammler S., Lykke-Andersen S., Christensen M.S., et al. (2008). RNA exosome depletion reveals transcription upstream of active human promoters. Science 322, 1851–1854. doi: 10.1126/science.1164096 19056938

26. Seila A.C., Calabrese J.M., Levine S.S., Yeo G.W., Rahl P.B., et al. (2008). Divergent transcription from active promoters. Science 322, 1849–1851. doi: 10.1126/science.1162253 19056940

27. Pefanis E., Wang J., Rothschild G., Lim J., Kazadi D. et al. (2015). RNA exosome-regulated long non-coding RNA transcription controls super-enhancer activity. Cell 161, 774–789. doi: 10.1016/j.cell.2015.04.034 25957685

28. Marin-Vicente C., Domingo-Prim J., Eberle A.B., Visa N. (2015). RRP6/EXOSC10 is required for the repair of DNA double-strand breaks by homologous recombination. J Cell Sci. 128, 1097–1107. doi: 10.1242/jcs.158733 25632158

29. Reyes-Turcu F.E., and Grewal S.I. (2012). Different means, same end-heterochromatin formation by RNAi and RNAi-independent RNA processing factors in fission yeast. Curr Opin Genet Dev 22, 156–163. doi: 10.1016/j.gde.2011.12.004 22243696

30. Reyes-Turcu F.E., Zhang K., Zofall M., Chen E., and Grewal S.I. (2011). Defects in RNA quality control factors reveal RNAi-independent nucleation of heterochromatin. Nature structural & molecular biology 18, 1132–1138.

31. Yamanaka S., Mehta S., Reyes-Turcu F.E., Zhuang F., Fuchs R.T., et al. (2013) RNAi triggered by specialized machinery silences developmental genes and retrotransposons. Nature 493, 557–560. doi: 10.1038/nature11716 23151475

32. Hessle V., von Euler A., Gonzalez de Valdivia E., and Visa N. (2012). Rrp6 is recruited to transcribed genes and accompanies the spliced mRNA to the nuclear pore. RNA 18, 1466–1474. doi: 10.1261/rna.032045.111 22745224

33. Tyagi A., Ryme J., Brodin D., Ostlund Farrants A.K., and Visa N. (2009). SWI/SNF associates with nascent pre-mRNPs and regulates alternative pre-mRNA processing. PLoS Genetics 5, e1000470. doi: 10.1371/journal.pgen.1000470 19424417

34. Hessle V., Bjork P., Sokolowski M., Gonzalez de Valdivia E., Silverstein R., et al. (2009). The exosome associates cotranscriptionally with the nascent pre-mRNP through interactions with heterogeneous nuclear ribonucleoproteins. Molecular biology of the cell 20, 3459–3470. doi: 10.1091/mbc.E09-01-0079 19494042

35. Lim S.J., Boyle P.J., Chinen M., Dale R.K., and Lei E.P. (2013). Genome-wide localization of exosome components to active promoters and chromatin insulators in Drosophila. Nucleic acids research 41, 2963–2980. doi: 10.1093/nar/gkt037 23358822

36. Kiss D.L., and Andrulis E.D. (2010). Genome-wide analysis reveals distinct substrate specificities of Rrp6, Dis3, and core exosome subunits. RNA 16, 781–791. doi: 10.1261/rna.1906710 20185544

37. Graham A.C., Kiss D.L., Andrulis E.D. (2009). Core exosome-independent roles for Rrp6 in cell cycle progression. Mol Biol Cell 20, 2242–2253. doi: 10.1091/mbc.E08-08-0825 19225159

38. Filion G.J., van Bemmel J.G., Braunschweig U., Talhout W., Kind J., et al. (2010). Systematic protein location mapping reveals five principal chromatin types in Drosophila cells. Cell 143, 212–224. doi: 10.1016/j.cell.2010.09.009 20888037

39. Petesch S.J., and Lis J.T. (2008). Rapid, transcription-independent loss of nucleosomes over a large chromatin domain at Hsp70 loci. Cell 134, 74–84. doi: 10.1016/j.cell.2008.05.029 18614012

40. Phillips S. and Butler J. S. (2003). Contribution of domain structure to the RNA 3' end processing and degradation functions of the nuclear exosome subunit Rrp6p. RNA. 9, 1098–1107.

41. Mendjan S., Taipale M., Kind J., Holz H., Gebhardt P., et al. (2006). Nuclear pore components are involved in the transcriptional regulation of dosage compensation in Drosphila. Mol Cell 21, 811–23 16543150

42. Yin H., and Lin H. (2007). An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster. Nature 450 : 304–308. 17952056

43. Richards E.J., and Elgin S.C. (2002). Epigenetic codes for heterochromatin formation and silencing: rounding up the usual suspects. Cell 108, 489–500. 11909520

44. Kiss D.L., and Andrulis E.D. (2011). The exozyme model: a continuum of functionally distinct complexes. RNA 17, 1–13. doi: 10.1261/rna.2364811 21068185

45. Bühler M., Spies N., Bartel D.P., and Moazed D. (2008). TRAMP-mediated RNA surveillance prevents spurious entry of RNAs into the Schizosaccharomyces pombe siRNA pathway. Nature structural & Molecular biology 15, 1015–1023.

46. Keller C., Kulasegaran-Shylini R., Shimada Y., Hotz H.R., and Bühler M. (2013). Noncoding RNAs prevent spreading of a repressive histone mark. Nature structural & molecular biology 20, 1340.

47. Lubas M., Christensen M.S., Kristiansen M.S., Domanski M., Falkenby L.G., et al. (2011). Interaction profiling identifies the human nuclear exosome targeting complex. Mol Cell 43, 624–37. doi: 10.1016/j.molcel.2011.06.028 21855801

48. Andersen P. R., Domanski M., Kristiansen M. S., Storvall H., Ntini E., et al. (2013). The human cap-binding complex is functionally connected to the nuclear RNA exosome. Nat Struct Mol Biol 20 : 1367–76. doi: 10.1038/nsmb.2703 24270879

49. Huang da W., Sherman B.T., and Lempicki R.A. (2009). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4, 44–57. doi: 10.1038/nprot.2008.211 19131956

50. Eberle A.B., Hessle V., Helbig R., Dantoft W., Gimber N., et al. (2010). Splice-site mutations cause Rrp6-mediated nuclear retention of the unspliced RNAs and transcriptional down-regulation of the splicing-defective genes. PLoS One 5, e11540. doi: 10.1371/journal.pone.0011540 20634951

51. Bustin S.A., Benes V., Garson J.A., Hellemans J., Huggett J., et al. (2009). The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 55, 611–622. doi: 10.1373/clinchem.2008.112797 19246619

52. Kim D., Pertea G., Trapnell C., Pimentel H., Kelley R., et al. (2013). TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 14(4), R36. doi: 10.1186/gb-2013-14-4-r36 23618408

53. Robinson J. T., Thorvaldsdóttir H., Winckler W., Guttman M., Lander E. S., et al. (2011) Integrative Genomics Viewer. Nature Biotechnology 29, 24–26. doi: 10.1038/nbt.1754 21221095

54. Eberle A.B., Bohm S., Ostlund Farrants A.K., and Visa N. (2012). The use of a synthetic DNA-antibody complex as external reference for chromatin immunoprecipitation. Anal Biochem 426, 147–152. doi: 10.1016/j.ab.2012.04.020 22543092